• What is the probability of having Phase 3 success, and is Phase 4 required?
  • Stockhead reached out to Cynata’s CMO, Dr Jolanta Airey
  • We look at ASX stocks with ongoing Phase 3 trials


In order to progress to the Phase 3 clinical trials, a drug must have demonstrated promising results in earlier Phase 1 and Phase 2 clinical trials.

In addition, a regulatory approval must be obtained to proceed to the larger, more comprehensive testing of Phase 3.

Phase 3 can involve thousands of patients, and is typically conducted at multiple clinical sites across different countries.

The primary goal of a Phase 3 trial is to confirm once again the efficacy and safety of the drug – this time on a wider population – and to provide the data necessary for regulatory and commercialisation approval.

Phase 3 trials are sometimes called registrational or pivotal trials.

But despite this generally accepted view, there is actually some flexibility around the requirements to progress through Phase 1, 2 and 3 etc. in sequence.

Dr Jolanta Airey, chief medical officer at Cynata Therapeutics (ASX:CYP) explained to Stockhead that the clinical trial of Cynata’s own CYP-004 product for osteoarthritis (OA) proceeded straight to Phase 3.

“This was largely due to the established safety profile, the design of the trial itself which was well powered with around 440 subjects and objective endpoints, and the clinical data using conventionally derived mesenchymal stem cells in OA.

But in general, the common next step after a successful Phase 3 trial is to submit a New Drug Application (NDA) to the FDA, in the case of the US.

In Australia, the drug company would submit what’s called a ‘marketing authorisation application’ to the Therapeutic Goods Administration (TGA) to seek approval to sell the drug in the country.


Is Phase 4 clinical trial needed?

In some instances, a Phase 4 clinical trial is conducted to gather more data on the drug’s safety, efficacy, and real-world use.

This extra information can help to identify any previously unknown side effects and confirm the drug’s effectiveness in different populations.

Airey explained that Phase 4 trials are not necessarily required, but if they are conducted, this happens after the product is launched on the market.

“Sometimes Phase 4 trials are necessary to satisfy a request from regulators as a condition of marketing approval,” she told Stockhead.

“And sometimes they are conducted voluntarily by the company marketing the product to generate further data to support sales and marketing activities.”

Because of that, Phase 4 trials are sometimes called post-marketing trials.

“Phase 4 also aims to investigate long term safety, drug effectiveness in real life conditions, study benefit risk profile in specific subset of patient population, or different drug combinations,” added Airey.


Probability of Phase 3 success

The probability of success in passing the pivotal Phase 3 trials would naturally be different for each drug.

“But in general, the development of new drugs is associated with risk, although the incremental probability of success increases with each developmental stage,” said Airey.

Overall, the probability of success in Phase 3 is about 60%.

Recent analyses indicate that the probability of success has improved over the past decade or so, likely due to better development strategies and study designs.

“An important factor in determining risk is whether there is prior clinical experience with the new drug or drug class,” Airey told Stockhead.

“For example, in Cynata’s situation, there is already a vast amount of clinical experience with mesenchymal stem cells (MSCs) attesting to their safety and efficacy.

“Thus, our Cymerus platform technology is supported by a thesis of lower development risk, because it is simply a better way to manufacture MSCs.”


Cynata’s Phase 3 trial in osteoarthritis

Cynata is currently undertaking a Phase 3 trial of CYP-004, the company’s MSC product for osteoarthritis.

Currently there is no cure for osteoarthritis and the relentlessly progressive nature of the disease, i.e. it keeps getting worse and often leads to costly, risky and invasive procedures such as joint replacement.

There have been many efforts to investigate new therapies and all of them have failed to demonstrate clinically meaningful efficacy.

Cynata’s ongoing Phase 3 study in association with the University of Sydney in mild to moderate knee OA is aiming to demonstrate not only improvement of the symptoms, but also slowing disease progression as measured by MRI.

“If successful, this will be the first study in the world to demonstrate disease modifying properties in OA,” said Airey.

“The regulators will probably want to see a second pivotal Phase 3 study or a post-marketing commitment to conduct an adequately powered Phase 4 in osteoarthritis.”


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Other ASX biotechs with ongoing Phase 3 trials


Neuren (ASX:NEU)

Neuren and Acadia Pharmaceuticals (Nasdaq: ACAD) announced positive top-line results from the pivotal, Phase 3 Lavender study evaluating the efficacy and safety of trofinetide in 187 girls and young women aged 5-20 years with Rett syndrome.

Acadia Pharma has submitted an application filing seeking FDA approval, which has been accepted and now being reviewed by the agency.

The FDA has set an action date of March 12, 2023 to decide whether or not to approve this experimental oral therapy trofinetide for Rett syndrome.


Dimerix (ASX:DXB)

Dimerix is undertaking a Phase III trial for its lead product DMX-200 in the study of rare kidney disease Focal Segmental  Glomerulosclerosis  (FSGS).

In January, the FDA confirmed that adolescent children, those aged between 12 to 17 years old, can be recruited to Dimerix’s ACTION3 global Phase 3 FSGS trial.

The ACTION 3 Phase 3 study is being performed across 75 sites, with part one data outcome expected to be known by mid-2023.


Opthea (ASX:OPT)

Eye disease specialist Opthea is conducting not one but two concurrent Phase 3 clinical trials with OPT-302 for the treatment of wet AMD, a chronic eye disorder that causes blurred vision or a blind spot in your visual field.

The Phase III trials, referred to as ShORe and COAST, are double-masked trials that have enrolled patients to assess the efficacy and safety of 2.0mg OPT-302 in combination with anti-VEGF-A therapy.


Telix Pharmaceuticals (ASX:TLX)

Oncology company Telix is a complex business with multiple trials and diagnostics.

In November, the company reported positive top line results from its ZIRCON Phase 3 study of imaging agent TLX250-CDx in clear cell renal cell carcinoma (ccRCC).

Telix reported that all of the primary and secondary endpoints in the study have been met.

The company says these “ground-breaking results” indicate that TLX250-CDx has the potential to become a new clinical standard in the diagnosis of ccRCC, and deliver an unmet medical need for a non-invasive diagnostic tool.


Invex Therapeutics (ASX:IXC)

In August last year, Invex received an FDA IND approval for Presendin, and for the commencement of the IIH EVOLVE Phase 3 clinical trial in the US for patients with idiopathic intracranial hypertension (IIH).

The Phase 3 trial is a placebo-controlled, double-blind trial that will randomise 240 patients with newly diagnosed IIH to determine the efficacy and safety of Presendin versus placebo.

Last month, Invex announced the opening of the company’s first US clinical site at the Eye Wellness Center in Bellaire, Texas to conduct this trial.


Paradigm Biopharmaceuticals (ASX:PAR)

Paradigm is conducting a Phase 3 trial in the US to support the registration of Pentosan Polysulfate Sodium (PPS) for osteoarthritis of the knee.

In December, the company announced that the first safety review meeting for this clinical trial has been conducted.

The Data Monitoring Committee (DMC) review concluded that the PARA_OA_002 clinical trial should proceed without modification.


Medlab Clinical (ASX:MDC)

Medlab is conducting Phase 3 trials for its lead asset cannabis based-pain medication NanaBis for cancer-related bone pain.

NanaBis is currently available for Australian patients under the Special Access Scheme (SAS), and launching in the UK under the Named Patient Program (NPP).

Last month, NanaBis (named NanaDol in the for UK) has been issued import certification by the UK Home Office.


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